Variant 2-227889870-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178821.3(DAW1):c.128C>T(p.Ala43Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000332 in 1,598,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

DAW1
NM_178821.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.69

Variant links:

Genes affected

DAW1 (HGNC:26383): (dynein assembly factor with WD repeats 1) Predicted to act upstream of or within several processes, including cerebrospinal fluid circulation; determination of left/right symmetry; and outer dynein arm assembly. Predicted to be located in cilium and extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

DAW1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14529097).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DAW1	NM_178821.3 linkuse as main transcript	c.128C>T	p.Ala43Val	missense_variant	3/13	ENST00000309931.3
DAW1	NM_001330004.2 linkuse as main transcript	c.83C>T	p.Ala28Val	missense_variant	4/14
DAW1	XM_047443536.1 linkuse as main transcript	c.83C>T	p.Ala28Val	missense_variant	5/15
DAW1	NR_138459.2 linkuse as main transcript	n.187C>T		non_coding_transcript_exon_variant	3/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAW1	ENST00000309931.3 linkuse as main transcript	c.128C>T	p.Ala43Val	missense_variant	3/13	1	NM_178821.3	P1	Q8N136-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000423

AC:

AN:

236134

Hom.:

AF XY:

0.00000783

AC XY:

AN XY:

127740

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000914

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000353

AC:

AN:

1446268

Hom.:

Cov.:

AF XY:

0.0000292

AC XY:

AN XY:

719176

show subpopulations

Gnomad4 AFR exome

AF:

0.0000308

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000133

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000325

Gnomad4 OTH exome

AF:

0.0000335

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152082

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.0000302

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2023

The c.128C>T (p.A43V) alteration is located in exon 3 (coding exon 3) of the DAW1 gene. This alteration results from a C to T substitution at nucleotide position 128, causing the alanine (A) at amino acid position 43 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

Cadd

Benign

Dann

Benign

0.94

DEOGEN2

Benign

0.0018

T;T

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.0085

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.87

N;N

REVEL

Benign

0.046

Sift

Benign

0.42

T;T

Sift4G

Benign

0.48

T;T

Polyphen

0.24

B;.

Vest4

0.19

MVP

0.65

MPC

0.090

ClinPred

0.34

GERP RS

4.6

Varity_R

0.056

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over